SHP-1 as a critical regulator of Mycoplasma pneumoniae-induced inflammation in human asthmatic airway epithelial cells

Ying Wang, Zhou Zhu, Tony D. Church, Njira L. Lugogo, Loretta G. Que, Dave Francisco, Jennifer L. Ingram, Molly Huggins, Denise M. Beaver, Jo Rae Wright, Monica Kraft

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Asthma is a chronic inflammatory disease in which airway epithelial cells are the first line of defense against exposure of the airway to infectious agents. Src homology protein (SHP)-1, a protein tyrosine phosphatase, is a negative regulator of signaling pathways that are critical to the development of asthma and host defense.We hypothesize that SHP-1 function is defective in asthma, contributing to the increased inflammatory response induced by Mycoplasma pneumoniae, a pathogen known to exacerbate asthma. M. pneumoniae significantly activated SHP-1 in airway epithelial cells collected from nonasthmatic subjects by bronchoscopy with airway brushing but not in cells from asthmatic subjects. In asthmatic airway epithelial cells, M. pneumoniae induced significant PI3K/Akt phosphorylation, NF-κB activation, and IL-8 production compared with nonasthmatic cells, which were reversed by SHP-1 overexpression. Conversely, SHP-1 knockdown significantly increased IL-8 production and PI3K/Akt and NF-κB activation in the setting of M. pneumoniae infection in nonasthmatic cells, but it did not exacerbate these three parameters already activated in asthmatic cells. Thus, SHP-1 plays a critical role in abrogating M. pneumoniae-induced IL-8 production in nonasthmatic airway epithelial cells through inhibition of PI3K/Akt and NF-κB activity, but it is defective in asthma, resulting in an enhanced inflammatory response to infection.

Original languageEnglish (US)
Pages (from-to)3371-3381
Number of pages11
JournalJournal of Immunology
Volume188
Issue number7
DOIs
StatePublished - Apr 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Wang, Y., Zhu, Z., Church, T. D., Lugogo, N. L., Que, L. G., Francisco, D., Ingram, J. L., Huggins, M., Beaver, D. M., Wright, J. R., & Kraft, M. (2012). SHP-1 as a critical regulator of Mycoplasma pneumoniae-induced inflammation in human asthmatic airway epithelial cells. Journal of Immunology, 188(7), 3371-3381. https://doi.org/10.4049/jimmunol.1100573